Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001235829 | SCV001408534 | uncertain significance | Frontotemporal dementia | 2019-07-15 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs149280278, ExAC 0.02%). This sequence change replaces valine with isoleucine at codon 287 of the MAPT protein (p.Val287Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant has been observed in individuals affected with Alzheimer's disease and frontotemporal dementia (PMID: 22906081, 27606344). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |